At present, cancers—characterized by anomalous cell proliferation—are diseases which are still most difficult to cure. Therefore, there is a keen demand for development of an effective drug for treating cancers. Since cell proliferation essentially involves biosynthesis of nucleic acid, hitherto, extensive studies have been carried out for developing nucleic acid metabolism antagonistic drugs which inhibit metabolism of nucleic acid.
Among these drugs, cytidine-derived nucleic acid metabolism antagonistic drugs have been developed by extensive studies. For example, cytarabine (Non-Patent Document 1), ancitabine (Non-Patent Document 2), cytarabine ocfosfate (Non-Patent Document 3), gemcitabine (Patent Document 1), etc. have been developed, and these drugs are now employed in clinical treatment.
These compounds exhibit an anti-tumor effect based on inhibition of DNA polymerase or ribonucleotide reductase, resulting in inhibition of DNA synthesis. These drugs attain clinical therapeutic results at a certain level. However, cytarabine, ancitabine, and cytarabine ocfosfate are known to have no activity to solid cancers (Non-Patent Document 4). In addition, gemcitabine can be applied to a very limited cancer type (Non-Patent Document 4). Thus, these drugs have never attained a satisfactory anti-tumor activity.
In order to solve the aforementioned problems, there has been developed 2′-cyano-2′-deoxy-1-β-D-arabinofuranosylcytosine (CNDAC) having a DNA strand breaking activity. An anti-tumor activity of CNDAC different from that of cytidine compounds which have been developed is envisaged (Patent Document 2 and Non-Patent Documents 5 and 6). In addition, 4-N-palmitoyl-2′-cyano-2′-deoxy-1-β-D-arabinofuranosylcytosine (P-CNDAC, Patent Document 3 and Non-Patent Documents 7 and 8), and 5′-phosphatidylpyrimidine nucleotide (Patent Document 4) have been developed as peroral drugs. These CNDAC compounds have been found to exhibit interesting anti-tumor effects (Non-Patent Documents 5 and 8).
However, these existing CNDAC compounds have not yet been on the market. Therefore, there is a keen demand for development and commercialization of cytidine-derived anti-tumor drugs exhibiting a more excellent anti-tumor effect and being perorally administrable.                [Patent Document 1] Japanese Patent Publication (kokoku) No. 6-37394        [Patent Document 2] Japanese Patent No. 2559917        [Patent Document 3] Japanese Patent No. 2569251        [Patent Document 4] Japanese Patent Application Laid-Open (kokai) No. 7-179491        [Non-Patent Document 1] Evance, J. S. et al. Proc. Soc. Exp. Bio. Med., 106, 350 (1961)        [Non-Patent Document 2] Hoshi, A. et al. Gann, 67, 725 (1972)        [Non-Patent Document 3] Kodama, K. et al. Jpn. J. Cancer Res., 80, to 685 (1989)        [Non-Patent Document 4] Matsuda, A., et al. Cancer Sci., 95, 105 to 111 (2004)        [Non-Patent Document 5] Matsuda, A., et al. J. Med. Chem., 34, 2919 to 2922 (1991)        [Non-Patent Document 6] Azuma, A., et al. J. Med. Chem., 36, 4183 to 4189 (1993)        [Non-Patent Document 7] Matsuda, Akira and Takuma, Sasaki, Protein, Nucleic Acid, and Enzyme, 43, 1981 to 1989 (1998)        [Non-Patent Document 8] Katz, M. H. et al. Cancer Res., 64, 1828 to 1833 (2004)        